Elevated oxygen extraction during heart transplantation is associated with increased morbidity and mortality: Implications for goal-directed perfusion

Background: Goal-directed perfusion (GDP) during cardiopulmonary bypass (CPB) commonly targets indexed oxygen delivery (DO2i), yet fixed delivery thresholds may ignore patient-specific metabolic demand. The oxygen extraction ratio (O2ER) integrates delivery and consumption and may better reflect supply–demand balance during heart transplantation. We evaluated whether intra-CPB O2ER burden is associated with adverse outcomes after adult heart transplantation and whether O2ER provides incremental prognostic value beyond DO2i. Methods: We retrospectively analyzed adult heart transplantations performed at a single center between November 2021 and June 2025. Minute-level CPB data were extracted. O2ER was the primary exposure, and the primary outcome was a composite morbidity–mortality (M-M) endpoint (severe primary graft dysfunction [PGD], ventilation for >72 hours, intensive care unit length of stay >15 days, renal replacement therapy, or 90-day mortality). Generalized propensity score–weighted logistic regression modeled associations adjusting for prespecified donor/recipient/procedural covariates. Comparative models assessed O2ER versus DO2i. A post hoc analysis quantified pre- and post-reperfusion O2ER area under the receiver operating characteristic curve (AUC) to localize phase-specific risk. Results: Among 381 heart transplant recipients, 40 (10.5%) experienced M-M. O2ER trajectories separated between the M-M and non–M-M groups during the mid-procedure window (∼35-100 minutes). Each additional 10 minutes at O2ER > 0.20 was associated with higher odds of M-M (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.00-1.15; P = .043) and 90-day mortality (OR, 1.13; 95% CI, 1.02-1.26; adjusted P = .02). Adding time at O2ER > 0.20 improved a DO2i < 280-only model (P = .04), whereas adding DO2i below-time to an O2ER-only model did not (P = .30). Phase-specific analysis showed that post-reperfusion O2ER AUC was independently associated with M-M (OR, 1.23; 95% CI, 1.08-1.40; P = .002) and severe PGD (OR, 1.22; 95% CI, 1.04-1.43; P = .01), while pre-reperfusion O2ER AUC was related to 90-day mortality (OR, 1.05; 95% CI, 1.004-1.10; P = .03). Conclusions: During heart transplantation, a higher O2ER burden on CPB is linearly associated with increased post-transplant morbidity and early mortality and contributes prognostic information beyond DO2i. These data support an O2ER-guided GDP strategy that minimizes time (or AUC) above O2ER thresholds, with heightened vigilance regarding reperfusion. Prospective validation is warranted.